The general purpose of this investigation is to elucidate mechanisms whereby neoplasms alter the biochemical and functional attributes of anatomically distant, apparently uninvolved tissues of the host organism. In response to the subcutaneously transplanted mammary and hepatocellular carcinomas studied, the enzymic composition of the liver becomes partially undifferentiated, and there are striking increases in the gamma-glutamyltranspeptidase and alkaline phosphatase activity of the bone marrow in lung as well as liver. The active principle(s) is of polypeptide nature; its purification and characterization are specific aims of the present project. Additional objectives are: (1)\to determine, using normal hepatocytes cultures, whether the diminution of hepatotypic enzymes is attributable to the same tumor-factors as is the rise of gamma-glutamyl-transpeptidase in the bone marrow and liver; (2)\to elucidate the underlying mechanisms and consequences of the increased gamma-glutamyltranspeptidase activity of granulocytes; and (3)\to examine the role of this enzyme in stimulated growth. (B)